title: Decreased PITX1 gene expression in human cutaneous malignant melanoma and its clinicopathological significance.
abstract: BACKGROUND
  The pituitary homeobox 1 (PITX1) protein is a member of the bicoid-related homeobox transcription factors and has essential roles in human development. Recently, the PITX1 gene has been considered as a tumor suppressor gene in various human cancers.
  
  
  OBJECTIVE
  This study examined the expression of PITX1 in the development and progression of human cutaneous malignant melanoma.
  
  
  METHODS
  Immunohistochemical and/or immunofluorescence analyses were performed to examine the histological expression of PITX1 in healthy skin and 40 cutaneous malignant melanoma cases, including 10 melanoma in situ cases.
  
  
  RESULTS
  Expression of PITX1 was shown in nuclei of melanocytes in normal skin. PITX1 expression was positive (labeling index: ≥10%) in 21 (52.5%) cases and negative (labeling index: <10%) in 19 (47.5%) of 40 cases of primary cutaneous malignant melanoma. The mean tumor thickness in PITX1-negative cases (7.11 ± 10.3 mm) was significantly higher than that in the positive cases (1.90 ± 3.19 mm) (P<0.01). The numbers of cases showing metastasis were 1 (4.76%) of 21 cases in PITX1-positive cases and 7 (36.8%) of 19 cases in PITX1-negative cases; the frequency was significantly higher in PITX1-negative cases than the positive cases (P = 0.012). Moreover, the reduction in PITX1 expression correlated significantly with clinical stage (P<0.001). Interestingly, PITX1 expression was inversely correlated with cell proliferation of cutaneous malignant melanoma (P<0.001).
  
  
  CONCLUSIONS
  Down-regulation of PITX1 expression might contribute to the progression of cutaneous malignant melanoma via promoting cell proliferative activity.
authors.affiliation: Division of Molecular Genetics and Biofunction, Institute of Regenerative Medicine and Biofunction,, Division of Pathological Biochemistry, Department of Biomedical Sciences.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Osaki
authors.affiliation: Division of Molecular Genetics and Biofunction, Institute of Regenerative Medicine and Biofunction.
authors.forename: Hikari
authors.initials: H
authors.lastname: Chinen
authors.affiliation: Division of Dermatology, Department of Medicine of Sensory and Motor Organs.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Division of Molecular Genetics and Biofunction, Institute of Regenerative Medicine and Biofunction.
authors.forename: Takahito
authors.initials: T
authors.lastname: Ohhira
authors.affiliation: Division of Molecular Genetics and Biofunction, Institute of Regenerative Medicine and Biofunction.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Sunamura
authors.affiliation: Division of Dermatology, Department of Medicine of Sensory and Motor Organs.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamamoto
authors.affiliation: Division of Organ Pathology, Department of Pathology, Tottori University Faculty of Medicine, 86 Nishi-cho Yonago, Tottori 683-8503, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
authors.affiliation: Division of Molecular Genetics and Biofunction, Institute of Regenerative Medicine and Biofunction.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
authors.affiliation: Division of Molecular Genetics and Biofunction, Institute of Regenerative Medicine and Biofunction.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kugoh
mesh_terms: D000368:Aged; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011379:Prognosis; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D051761:Paired Box Transcription Factors; C101485:homeobox protein PITX1
keywords: Ki-67; PITX1; malignant melanoma; tumor progression